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The William Harvey Research Institute - Barts and The London

Professor Alberto Mantovani

Alberto

Chair of Inflammation and Therapeutic Innovation

Email: a.mantovani@qmul.ac.uk

Profile

Alberto Mantovani, MD, is Professor of Pathology at Humanitas University in Milan, and Scientific Director of the Istituto Clinico Humanitas.  His attention has been focused on molecular mechanisms of innate immunity and inflammation. He has contributed to the advancement of knowledge in the field of Immunology and Oncology formulating new paradigms and identifying new molecules and functions.

For his research activity he has received several national and international awards, such as the Triennial OECI Award from the Organization of the European Cancer Institutes,  the Robert Koch Award for his contribution to tumor immunology and immunotherapy, the American-Italian Cancer Foundation (AICF) Prize for Excellence in Medicine and, most recent, the American Association for Cancer Research International Pezcoller Award for Extraordinary Achievement in Cancer Research. The broad impact of his contributions is testified by citations.  As of January 2019 he has over 111,000 (Scopus), 80,000 (Web of Science) or 160,000 (Google Scholar) citations and an H-index of 161 (Scopus), 125 (Web of Science) or 185 (Google Scholar).   

Selected major honors

National or International awarded in Italy

1998: Biotec Award
2004: Guido Venosta Award for Cancer Research by the President of the Republic of Italy
2005: Premio Ippocrate per la Ricerca Biomedica
2006: “Onorificenza al Merito della Repubblica Italiana”  (Commendatore, knightwood equivalent) for scientific contribution by the President of  the Republic of Italy
2007: Galileo Galilei Prize for Research in Biomedical Sciences (International Jury)
2012: Premio Nazionale "L'Altra Italia ... Vite da Premio"
2014: Premio Rosa Camuna 2014, Regione Lombardia
2015: Ferrari-Soave International Prize, Accademia delle Scienze, Torino.
2016: NIBIT Award, Siena
2016: Premio Roma allo Sviluppo del Paese.
2016: International Feltrinelli Prize from the Accademia dei Lincei.
2017: Premio Scanno, Fondazione Tanturri, Scanno, Italy.
2018: Medaglia d’Oro di Benemerenza Civica, Milan Municipality (Ambrogino d’Oro).

International

2000: Marie T. Bonazinga Award, Society for Leukocyte Biology, Boston, USA
2006: European Federation of Immunological Societies – Schering Plough, 1st European Immunology Prize, Paris, France
2009: William Harvey Award, Oustanding Scientist 2009, London, UK.
2015: European Society for Clinical Investigation Albert Struyvenberg Medal
2015: The Milstein Award for Excellence in Interferon and Cytokine Research, International Cytokine & Interferon Society. 
2016: OECI (Organization of European Cancer Institutes) Prize for contribution to Cancer Immunology and Immunotherapy. OECI awards the OECI Prize every three years.
2016: Robert Koch Award, Robert Koch Stiftung, Germany
2017:  Journal of Autoimmunity dedicated Issue to Alberto Mantovani
2018: American-Italian Cancer Foundation (AICF, New York) Prize for Excellence in Medicine.
2019: American Association for Cancer Research International Pezcoller Award for Extraordinary Achievement in Cancer Research.
2019:  ITOC6 – 6th Immunotherapy of Cancer Conference Lifetime Achievement Award

Selected memberships, boards and academies

1995-1998: President, Italian Federation of Immunological Societies
1998-2001: President, Italian Society of Immunology
2000 to date: European Molecular Biology Organization (EMBO) Member
2002: Member, The Henry Kunkel Society
2003: Co-founder and President (2011-2012) of Gruppo 2003, the association of Italian highly cited  scientists to promote Science awareness in Italy
2005-2010: Board Member of the Global Alliance for Vaccines and Immunization (GAVI Alliance)
2008: Member, Faculty of 1000 Biology
2009-2010: President, International Cytokine Society
2011-2013: Board Member, International Union of Immunological Societies (IUIS)
2013-2016: Vice-President/President Elect, International Union of Immunological Societies (IUIS)
2016: Member, Accademia dei Lincei, Rome, Italy
2016: Member, Robert Koch Stiftung, Berlin                                                                                           
2016-2019: President, International Union of Immunological Societies (IUIS)
2017: Member, Academia Europaea
2017: Honorary Member, Scandinavian Society of Immunology

Research

Tumor-associated macrophages (TAM).  Demonstration in the late ‘70s of the protumor function of tumor-associated macrophages  (TAM, an acronym now generally used and coined by him in the ‘70s)  linking inflammation and cancer (reviewed in Balkwill and Mantovani, Lancet, 2001). TAM as an M2-like population (Bottazzi et al, Science 1983; Mantovani et al., Nature 2008; Balkwill et al., Cancer Cell 2005).  Promotion of tumor progression by IL-1 (Cancer Res. 1990; 1993). First linking of a genetic event (RET/PTC rearrangement)  causing cancer in humans to the construction of an inflammatory microenvironment (Borrello et al., PNAS 2005). Proof of principle that targeting tumor promoting macrophages has therapeutic value in humans (Germano et al, Cancer Cell 2013). Demonstration that PTX3 is an extrinsic oncosuppressor regulating Complement and macrophage-driven tumor promoting inflammation (Bonavita et al Cell 2015). Alberto Mantovani is recognized among his peers as a forerunner in the ‘70s and a “founding father” of the renaissance of the inflammation-cancer connection. For IL-1R8, see below, IL-1.

Chemokines. Description and role in TAM recruitment of a unique monocyte attractant, Monocyte Chemotactic Protein-1 (CCL2), as tumor-derived chemotactic factor (Bottazzi et al, Science 1983). Characterization of chemokines and role in pathophysiology, including dendritic cell and polarized T cell migration. Induction of chemokine production by IL-6 in endothelial cells via trans-signaling, a key component of chronic inflammation and cancer (Romano et al, Immunity 1997). Characterization of D6 as a decoy receptor for inflammatory CC chemokines (Mantovani et al, Nature Rev. Immunol 2006). Role of chemokines in carcinogenesis (for a recent contribution Bonavita et al Cell 2015). Role of the chemokines vMIPs in attracting Th2 cells and role of D6 (ACKR2) in Kaposi’s sarcoma.

IL-1/Toll-like receptors (TLR). Endothelial cell activation by IL-1 and cytokines (Rossi et al., Science 1985; Bussolino et al, Nature 1989; Romano et al, Immunity 1997). Identification of the type II receptor as a decoy receptor, a novel concept in biology (Colotta et al, Science 1993); the discovery of a decoy receptor represented a paradigm shift after the original definition of the concept of “receptor” by Langley in the 1930’; decoy receptors are now recognized as a general,  evolutionary conserved strategy to tune cytokines, chemokines and growth factors. Cloning of an intracellular isoform of the IL-1 receptor antagonist (Muzio et al., J. Exp. Med.  1995). First demonstration of MyD88 as the adaptor of mammalian Toll-Like Receptors (TLR) and identification of downstream transducers (Muzio et al., J. Exp. Med. 1998). Cloning and characterization of TIR8/SIGIRR (IL-1R8), a negative regulator of IL-1 receptor and TLR signalling (Garlanda et al, Immunity 2013). Role in carcinogenesis. In NK cells IL-1R8 serves as a checkpoint: its blocking unleashes resistance to carcinogenesis and metastasis at selected anatomical sites (Molgora et al, Nature 2017).

Humoral innate immunity: cloning (cDNA and genomic, mouse and human), structural and functional characterization of the first long pentraxin PTX3 as an IL-1 inducible gene (Garlanda et al, Nature 2002; Jeannin et al, Immunity 2005; Jaillon et al. J. Exp Med 2007 ; Deban et al, Nature Immunol. 2010; Jaillon et al. Immunity 2014; Bonavita et al. Cell 2015); structural immunobiology; role as a paradigm for humoral innate immunity; role as an extrinsic oncosuppresor in murine and human tumors regulating Complement and macrophage driven tumor promoting inflammation (Bonavita et al. Cell 2015); diagnostic and therapeutic translation (Cunha et al New England J. Med. 2014; ongoing). Thus, a regulator of macrophage-driven tumor promoting inflammation is a bona fide cancer gene, silenced in selected human tumors such as colorectal cancer, a finding now independently confirmed in large patients cohorts.

 

Key Publications

Originals

  • Mattiola I, Tomay F, De Pizzol M, Silva-Gomes R, Savino B , Gulic T, Doni A , Lonardi S , Boutet MA , Nerviani A, Carriero R , Molgora M , Stravalaci M, Morone D, Shalova IN, Lee Y, Biswas SK, Mantovani G, Sironi M, Pitzalis C, Vermi W, Bottazzi B, Mantovani A*, Locati M*. The interplay of the macrophage tetraspan MS4A4A with Dectin-1 and its role in NK cell-mediated resistance to metastasis. (*corresponding authors). Nature Immunol, in press.
  • Molgora M, Bonavita E, Ponzetta A, Riva F, Barbagallo M, Jaillon S, Popovic B, Bernardini G, Magrini E, Gianni F, Zelenay S, Jonjic S, Santoni A, Garlanda C, Mantovani A. IL-1R8 is a checkpoint in NK cells regulating anti-tumor and anti-viral activity. Nature, 551:110-114, 2017.
  • Doni A, Musso T, Morone D, Bastone A, Zambelli V, Sironi M, Castagnoli C, Cambieri I, Stravalaci M, Pasqualini F, Laface I, Valentino S, Tartari S, Ponzetta A, Maina V, Barbieri SS, Tremoli E, Catapano AL, Norata GD, Bottazzi B, Garlanda C, Mantovani A. An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode. J Exp Med.  212: 905-925, 2015.
  • Bonavita E, Gentile S, Rubino M, Maina V, Papait R, Kunderfranco P, Greco C, Feruglio F, Molgora M, Laface I, Tartari S, Doni A, Pasqualini F, Barbati E, Basso G, Galdiero MR, Nebuloni M, Roncalli M, Colombo PG, Laghi L, Lambris JD, Jaillon S, Garlanda C, Mantovani A.  PTX3 is an extrinsic oncosuppressor regulating complement-dependent inflammation in cancer. Cell  160: 700-714, 2015.
  • Jaillon S,  Moalli F,  Ragnarsdottir B, Bonavita E, Riva F, Barbati E, Nebuloni M, Krajinovic LC, Markotic A, Valentino S, Doni A, Tartari S, Graziani G, Montanelli A, Delneste Y, Svanborg C, Garlanda C, Mantovani A.  The humoral pattern recognition molecule PTX3 is a key component of innate immunity against urinary tract infection. Immunity 40: 621-632, 2014.
  • Cunha C, Aversa F, Lacerda JF, Busca A, Kurzai O, Grube M, Löffler J, Maertens JA,  Bell AS, Inforzato A, Barbati E, Almeida B, Santos e Sousa P, Barbui A, Potenza L, Caira M, Ph.D., Rodrigues F, Salvatori G, Pagano L, Luppi M, Mantovani A,Velardi A, Romani L, Carvalho A.  Genetic deficiency of PTX3 and aspergillosis in stem cell transplantation. New Engl J Med, 370:421-432, 2014.
  • Germano G, Frapolli R, Belgiovine C, Anselmo A, Pesce S, Liguori M, Erba E, Uboldi S, Zucchetti M, Pasqualini F, Nebuloni M, van Rooijen N, Mortarini R, Beltrame L, Marchini S, Fuso Nerini I, Sanfilippo R, Casali PG, Pilotti S, Galmarini CM, Anichini A, Mantovani A, D'Incalci M, Allavena P. Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell 23: 249-262, 2013.
  • Deban L, Castro Russo R, Sironi M, Moalli F, Scanziani M, Zambelli V, Cuccovillo I, Bastone A, Gobbi M, Valentino S, Doni A, Garlanda C, Danese S, Salvatori G, Sassano M, Evangelista V, Rossi B,  Zenaro E, Constantin G, Laudanna C, Bottazzi B, Mantovani A Regulation of leukocyte recruitment by the long pentraxin PTX3.  Nature Immunol, 11: 328-334, 2010.
  • Di Liberto D, Locati M, Caccamo N, Vecchi A, Meraviglia S, Salerno A, Sireci G, Nebuloni M, Cardona P-J, Dieli F, Mantovani A.  Role of the chemokine decoy receptor D6 in balancing inflammation, immune activation and antimicrobial resistance in Mycobacterium tuberculosis infection.  J. Exp. Med. 205: 2075-2084, 2008.
  • Lech M,Kulkarni OP, Pfeiffer S, Savarese E, Krug A, Garlanda C, Mantovani A, Anders H-J  Tir8/Sigirr prevents murine lupus by suppressing the immunostimulatory effects of lupus autoantigens.  J. Exp. Med. 205: 1879-1888, 2008.
  • Jaillon S, Peri G, Delneste Y, Frèmaux I, Doni A, Moalli F, Garlanda C, Romani L, Gascan H, Bellocchio S, Bozza S, Cassatella MA, Jeannin P, Mantovani A.  The humoral pattern recognition receptor PTX3 is stored in neutrophil granules and localized in extracellular traps.   J. Exp. Med., 204, 793-804, 2007.
  • Martinez de la Torre Y, Buracchi C, Borroni EM, Dupor J,  Bonecchi R, Nebuloni M, Pasqualini F, Doni A, Lauri E et al.  Protection against inflammation- and autoantibody- caused fetal loss by the chemokine decoy receptor D6. PNAS 104:2319-2324, 2007.
  • Biswas SK, Gangi L, Paul S, Schioppa T, Saccani A, Sironi M, Bottazzi B, Doni A, Vincenzo B, Pasqualini F, Vago L, Nebuloni M, Mantovani A*, Sica A. (* corresponding author). A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappaB and enhanced IRF-3/STAT1 activation). Blood 107:2112-2122, 2006.
  • Borrello MG, Alberti L, Fischer A, Degl’InnocentiD, Ferrario C, Gariboldi M, Marchesi F, Allavena P, Greco A, Collini P, Pilotti S, Cassinelli G, Bressan P, Fugazzola L, Mantovani A*, Pierotti M*  (*corresponding authors).  Induction of a proinflammatory programme in normal human thyrocytes by the RET/PTC1 oncogene.  PNAS, 102:  14825-14830, 2005.
  • Jeannin P., Bottazzi B., Sironi M., Doni A., Rusnati M., Presta M., Maina V., Magistrelli G., Haeuw J.F., Hoeffel G., Thieblemont N., Corvaia N., Garlanda C., Delneste Y., Mantovani A.  Complexity and complementarity of outer membrane protein-A recognition by cellular and humoral innate immunity receptors  Immunity 22: 551-560, 2005.

Reviews

  • Locati M, Curtale G, Mantovani A Diversity, mechanisms and significance of macrophage plasticity. Annu. Rev. Pathol, in press
  • Mantovani A, Dinarello CA, Molgora M, Garlanda C. IL-1 and related cytokines in innate and adaptive immunity in health and disease. Immunity, in press.
  • Mantovani A., Marchesi F., Laghi L., Malesci A., Allavena P.   Tumor-associated macrophages as treatment targets in oncology. Nature Rev, Clin. Oncol. 14(7):399-416, 2017.
  • Mantovani A, Allavena P. The interaction of anticancer therapies with tumor-associated macrophages. J Exp Med. 2015 Apr 6;212(4):435-445.
  • Garlanda C., Dinarello C.A.,  Mantovani A. The IL-1 family: back to the future. Immunity 39: 1003-1018, 2013.
  • Locati M.,  Mantovani A., Sica A. Macrophage activation and polarization as an adaptive component of innate immunity. Adv. Immunol. 120: 163-184, 2013
  • Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest. 122: 787-795, 2012.
  • Biswas S.K. and  Mantovani A. Orchestration of metabolism by macrophages. Cell Metab. 15: 432-437, 2012.
  • Mantovani A, Cassatella MA, Costantini C, Jaillon S. Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol. 11: 519-531, 2011.
  • Biswas S.K. and  Mantovani A.  Macrophage plasticity and interaction with lymphocyte subsets: cancer as paradigm. Nat Immunol 11: 889-896, 2010.
  • Bottazzi B, Doni A, Garlanda C, Mantovani A. An Integrated View of Humoral Innate Immunity: Pentraxins as a Paradigm. Annu Rev Immunol. 28:157-183, 2010.
  • Garlanda C, Anders HJ, Mantovani A.TIR8/SIGIRR: an IL-1R/TLR family member with regulatory functions in inflammation and T cell polarization.Trends Immunol. 30: 439-446, 2009.
  • Mantovani A. Cancer: Inflaming metastasis. Nature 45: 36-37, 2009.
  • Mantovani A, Allavena P, Sica A, Balkwill F  Cancer-Related Inflammation. Nature 454: 436-444, 2008.
  • Mantovani, A., Romero, P., Paluka, AK., Marincola, FM.  Tumor immunity: effector response to tumor and the influence of the microenvironment. Lancet 371:771-783, 2008.
  • Mantovani A, Bonecchi R, Locati M.  Tuning inflammation and immunity by chemokine sequestration: decoys and more. Nature Rev. Immunol. 6: 907-918, 2006.
  • Balkwill F, Charles KA, Mantovani A. Smouldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 7: 211-217, 2005.
  • Garlanda C.,  Bottazzi B., Bastone A.,  Mantovani A., Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility Annu. Rev. Immunol., 23: 337-366, 2005.

 

 

 

News

Contribution to Public Awareness of Science

Alberto Mantovani has been actively involved in the fostering of science and scientific policies in Italy at various levels, with a focus on Immunology, Vaccines, Oncology and Public Health, taking public stands on several issues including quackery whenever appropriate. He regularly contributes to the most authoritative italian daily newspapers (eg Corriere della Sera; La Repubblica; La Stampa; Il Sole 24 Ore) and magazines (Espresso and Panorama). He wrote four books on Immunology and Science targeted to the lay public (I Guardiani della Vita, Baldini e Castoldi, 2011; Immunità e Vaccini, Mondadori, 2016;  Non avere Paura di Sognare, La Nave di Teseo, 2016; Bersaglio Mobile, Mondadori, 2018). He contributed to scientific (eg SuperQuark; TGR Leonardo; Radio Tre Scienza Scienza) and general radio (e.g. Radio Tre Scienza) and television (e.g. Geo; Che Tempo che Fa) programs. To promote science awareness and policy he cofounded the association “ Gruppo2003” of Italian highly cited scientists (http://www.gruppo2003.it) and together with astrophysicist Tommaso Maccacaro founded the website http://www.scienzainrete.it.